Effect of Recombinant Human Growth Hormone and Rosiglitazone for HIV-Associated Abdominal Fat Accumulation on Adiponectin and other Markers of Inflammation.

BACKGROUND/OBJECTIVE: In a previous report of HIV-infected patients with fat redistribution, we found that recombinant human growth hormone (rhGH) therapy reduced visceral adipose tissue (VAT) but increased insulin resistance, and that the addition of rosiglitazone reversed the negative effects of rhGH on insulin sensitivity. In this study, we sought to determine the effects of rhGH and rosiglitazone therapy on an array of inflammatory and fibrinolytic markers. METHODS: 72 patients with HIV-associated abdominal obesity and insulin resistance were randomized to treatment with rhGH, rosiglitazone, the combination of rhGH and rosiglitazone, or placebo for 12 weeks. Subjects with plasma and serum samples available at weeks 0 (n=63) and 12 (n=46-48) were assessed for adiponectin, C-reactive protein, homocysteine, interleukin-1, interleukin-6, tumor necrosis factor alpha, interferon gamma, fibrinogen, plasminogen activator inhibitor-1 antigen, and tissue plasminogen activator antigen. RESULTS: Treatment with both rosiglitazone alone and the combination of rosiglitazone and rhGH for 12 weeks resulted in significant increases in adiponectin levels from baseline. Adiponectin levels did not change significantly in the rhGH arm alone . There were no significant changes in the other biomarkers among the different treatment groups. DISCUSSION: In this study of HIV-infected patients with altered fat distribution, treatment with rosiglitazone had beneficial effects on adiponectin concentrations, an effect that was also seen with a combination of rosiglitazone and rhGH. RhGH administration alone, however, did not demonstrate any significant impact on adiponectin levels despite reductions in VAT.

The effect of recombinant human growth hormone with or without rosiglitazone on hepatic fat content in HIV-1-infected individuals: a randomized clinical trial.

BACKGROUND: Hepatic fat is related to insulin resistance (IR) and visceral adipose tissue (VAT) in HIV+ and uninfected individuals. Growth hormone (GH) reduces VAT but increases IR. We evaluated the effects of recombinant human GH (rhGH) and rosiglitazone (Rosi) on hepatic fat in a substudy of a randomized controlled trial. METHODS: HIV+ subjects with abdominal obesity and IR (QUICKI≤0.33) were randomized to rhGH 3 mg daily, Rosi 4 mg twice daily, the combination or double placebo. Hepatic fat was measured by magnetic resonance spectroscopy, visceral fat by MRI and IR by frequently sampled intravenous glucose tolerance tests at baseline and week 12. RESULTS: 31 subjects were studied at both time points. Significant correlations between hepatic fat and VAT (r=0.41; P=0.02) and QUICKI (r=0.39; P<0.05) were seen at baseline. IR rose with rhGH but not Rosi. When rhGH treatment groups were combined, hepatic fat expressed as percentage change decreased significantly (P<0.05) but did not change in Rosi (P=0.71). There were no correlations between changes in hepatic fat and VAT (P=0.4) or QUICKI (P=0.6). In a substudy of 21 subjects, a trend was noticed between changes in hepatic fat and serum insulin-like growth factor-1 (IGF-1; P=0.09). CONCLUSIONS: Hepatic fat correlates significantly with both VAT and IR, but changes in hepatic fat do not correlate with changes in VAT and glucose metabolism. Hepatic fat content is reduced by rhGH but Rosi has no effect. These results suggest an independent effect of GH or IGF-1 on hepatic fat. The study was registered at Clinicaltrials.gov (NCT00130286).

Effect of Gender on the Response to Hepatitis C Treatment in an Inner-City Population.

INTRODUCTION: Hepatitis C virus (HCV) is the leading cause of cirrhosis, hepatocellular carcinoma, and liver transplantation in the United States. Response to treatment has improved with the addition of direct acting protease inhibitors. However, there are limited real-world data on the role of gender in achieving a sustained virologic response (SVR). METHODS: We conducted a cross-sectional study in 70 patients treated for HCV, genotype 1 infection with pegylated alpha interferon, ribavirin, and either telaprevir or boceprevir at our inner-city liver clinic. RESULTS: The SVR was significantly lower in women than in men (24% vs. 59%; p < .01). Statistical significance persisted after adjusting for age, race, genotype, prior treatment status, duration of therapy, and stage of fibrosis. The adjusted odds ratio for achieving SVR was significantly lower in women than in men (odds ratio [OR], 0.13; 95% CI, 0.03-0.58; p = .01). Relapse after completing treatment was more likely to occur in women (p = .02). Thirty-four patients (48%) did not complete therapy. Discontinuation because of loss to follow-up was more likely in women, whereas discontinuation owing to therapy limiting adverse drug events were more common in men. Discontinuation rates owing to failure of therapy were similar in men and women. CONCLUSIONS: There was a significant difference in SVR between men and women. Both biological and nonbiological factors, the latter including access to care, adherence to therapy, and attitudes of and toward health care providers all could play a role in contributing to the observed disparity between sexes in treatment response.

Relative effects of heavy alcohol use and hepatitis C in decompensated chronic liver disease in a hospital inpatient population.

BACKGROUND: Heavy alcohol use has been hypothesized to accelerate disease progression to end-stage liver disease in patients with hepatitis C virus (HCV) infection. In this study, we estimated the relative influences of heavy alcohol use and HCV in decompensated chronic liver disease (CLD). METHODS: Retrospectively, 904 patients with cirrhotic disease admitted to our hospitals during January 2010-December 2012 were identified based on ICD9 codes. A thorough chart review captured information on demographics, viral hepatitis status, alcohol use and progression of liver disease (i.e. decompensation). Decompensation was defined as the presence of ascites due to portal hypertension, bleeding esophageal varices, hepatic encephalopathy or hepatorenal syndrome. Heavy alcohol use was defined as a chart entry of greater than six daily units of alcohol or its equivalent. RESULTS: 347 patients were included based on our selection criteria of documented heavy alcohol use (n = 215; 62.0%), hepatitis titers (HCV: n = 182; 52.5%) and radiological evidence of CLD with or without decompensation (decompensation: n = 225; 64.8%). Independent of HCV infection, heavy alcohol use significantly increased the risk of decompensation (OR = 1.75, 95% CI 1.11-2.75, p < 0.02) relative to no heavy alcohol use. No significance was seen with age, sex, race, HIV, viral hepatitis and moderate alcohol use for risk for decompensation. Additionally, dose-relationship regression analysis revealed that heavy, but not moderate alcohol use, resulted in a three-fold increase (p = 0.013) in the risk of decompensation relative to abstinence. CONCLUSIONS: While both heavy alcohol use and HCV infection are associated with risk of developing CLD, our data suggest that heavy, but not moderate, alcohol consumption is associated with a greater risk for hepatic decompensation in patients with cirrhosis than does HCV infection.

Treatment of chronic hepatitis C virus infection in the United States: some remaining obstacles.

Hepatitis C infection is an important problem in inner city neighbourhoods, which suffer from multiple health disparities. Important factors in this population include alcoholism and substance abuse, mental illness and homelessness, which may be combined with mistrust, poor health literacy, limited access to healthcare and outright discrimination. Systemic barriers to effective care include a lack of capacity to provide comprehensive care, insufficient insurance coverage, poor coordination among caregivers and between caregivers and hospitals, as well as third party payers. These barriers affect real world treatment effectiveness as opposed to treatment efficacy, the latter reflecting the world of clinical trials. The components of effectiveness include efficacious medications, appropriate diagnosis and evaluation, recommendation for therapy, access to therapy, acceptance of the diagnosis and its implications by the patient and adherence to the recommended therapy. Very little attention has been given to assisting the patient to accept the diagnosis and adhere to therapy, i.e. care coordination. For this reason, care coordination is an area in which greater availability could lead to greater acceptance/adherence and greater treatment effectiveness.

Recombinant human growth hormone and rosiglitazone for abdominal fat accumulation in HIV-infected patients with insulin resistance: a randomized, double-blind, placebo-controlled, factorial trial.

BACKGROUND: Recombinant human growth hormone (rhGH) reduces visceral adipose tissue (VAT) volume in HIV-infected patients but can worsen glucose homeostasis and lipoatrophy. We aimed to determine if adding rosiglitazone to rhGH would abrogate the adverse effects of rhGH on insulin sensitivity (SI) and subcutaneous adipose tissue (SAT) volume. METHODOLOGY/PRINCIPAL FINDINGS: Randomized, double-blind, placebo-controlled, multicenter trial using a 2×2 factorial design in which HIV-infected subjects with abdominal obesity and insulin resistance were randomized to rhGH 3 mg daily, rosiglitazone 4 mg twice daily, combination rhGH + rosiglitazone, or double placebo (control) for 12 weeks. The primary endpoint was change in SI by frequently sampled intravenous glucose tolerance test from entry to week 12. Body composition was assessed by whole body magnetic resonance imaging (MRI) and dual Xray absorptiometry (DEXA). Seventy-seven subjects were randomized of whom 72 initiated study drugs. Change in SI from entry to week 12 differed across the 4 arms by 1-way ANCOVA (P = 0.02); by pair-wise comparisons, only rhGH (decreasing SI; P = 0.03) differed significantly from control. Changes from entry to week 12 in fasting glucose and glucose area under the curve on 2-hour oral glucose tolerance test differed across arms (1-way ANCOVA P = 0.004), increasing in the rhGH arm relative to control. VAT decreased significantly in the rhGH arms (-17.5% in rhGH/rosiglitazone and -22.7% in rhGH) but not in the rosiglitazone alone (-2.5%) or control arms (-1.9%). SAT did not change significantly in any arm. DEXA results were consistent with the MRI data. There was no significant rhGH x rosiglitazone interaction for any body composition parameter. CONCLUSIONS/SIGNIFICANCE: The addition of rosiglitazone abrogated the adverse effects of rhGH on insulin sensitivity and glucose tolerance while not significantly modifying the lowering effect of rhGH on VAT. TRIAL REGISTRATION: Clinicaltrials.gov NCT00130286.

Effect of supplementation with cholecalciferol and calcium on 2-y bone mass accrual in HIV-infected children and adolescents: a randomized clinical trial.

BACKGROUND: Skeletal abnormalities have been reported in HIV-infected children and adolescents. Although the etiology is not well understood, vitamin D deficiency may be involved. OBJECTIVE: The study objective was to evaluate the effect of vitamin D and calcium supplementation on bone mass accrual in HIV-infected youth. DESIGN: Perinatally HIV-infected children were randomly assigned to receive vitamin D (100,000 IU cholecalciferol given every 2 mo) and calcium (1 g/d) (supplemented group) or double placebo (placebo group) for 2 y. The total-body bone mineral content (TBBMC), total-body bone mineral density (TBBMD), spine bone mineral content (SBMC), and spine bone mineral density (SBMD) were assessed by using dual-energy X-ray absorptiometry at baseline and at 2 annual follow-up visits. RESULTS: Fifty-nine participants, aged 6-16 y, were randomly assigned to either the supplemented (n = 30) or the placebo (n = 29) group. At enrollment, supplemented and placebo groups did not differ with respect to age, sex, dietary intakes of vitamin D and calcium, mean baseline serum 25-hydroxyvitamin D [25(OH)D] concentration, TBBMC, TBBMD, SBMC, or SBMD. Significant increases in serum 25(OH)D were observed in the supplemented group but not in the placebo group. TBBMC, TBBMD, SBMC, and SBMD increased significantly at 1 and 2 y in both groups. No between-group differences were observed at any time before or after adjustment for stage of sexual maturation by mixed linear model analysis. CONCLUSION: One gram of calcium per day and oral cholecalciferol at a dosage of 100,000 IU every 2 mo administered to HIV-infected children and adolescents did not affect bone mass accrual despite significant increases in serum 25(OH)D concentrations. This trial was registered at clinicaltrials.gov as NCT00724178.

Longitudinal changes in regional fat content in HIV-infected children and adolescents.

BACKGROUND: Alterations in regional fat are often reported in HIV infection. Prior studies have not distinguished between normal changes in regional fat related to sexual maturation and those due to HIV. The study aim was to compare changes in regional fat distribution in HIV-infected (HIV+) and healthy (HIV-) children and adolescents living in the United States. METHODS: Serial dual energy X-ray absorptiometry was performed at baseline and two annual follow-up visits in 64 HIV+ and 147 HIV--participants aged 6-16 years. Total, leg, arm, and trunk fat masses (kg) and regional fat distribution as the percentage of total body fat (%) were compared. RESULTS: HIV+ and HIV--participants did not differ in total fat mass, but the HIV+ group had significantly lower leg and greater arm fat and trunk fat percentage at all time points. Over time, decreases in leg fat percentage and increases in arm fat percentage were more marked among the HIV+ group. Differences between HIV+ and HIV--groups in arm and leg fat percentage remained significant when age, sex, race, height, and pubertal stage were accounted for by mixed effect modeling. Apart from prior treatment with stavudine, no differences in fat distribution were observed according to treatment or degree of immunodeficiency or viremia. CONCLUSION: Although no single pattern of change in regional fat distribution was uniquely associated with HIV, perinatally HIV-infected youth manifest significantly decreased leg fat and increased arm and trunk fat. These differences increase over time and may contribute to cardiovascular disease risk.

Effect of bimonthly supplementation with oral cholecalciferol on serum 25-hydroxyvitamin D concentrations in HIV-infected children and adolescents.

OBJECTIVE: Vitamin D insufficiency occurs commonly in HIV-infected youth in the United States. In light of the importance of vitamin D for skeletal and nonskeletal health, including innate immunity, developing methods for improving vitamin D status in HIV-infected children and adolescents is an important area of clinical research. The objective of this study was to evaluate the effect of administration of oral cholecalciferol, 100,000 IU every 2 months, and 1 g/day calcium on serum 25-hydroxyvitamin D concentrations, serum and urine calcium, and HIV disease progression during a 12-month period. METHODS: HIV-infected children and adolescents who were aged 6 to 16 years were randomly assigned to receive vitamin D (100,000 IU bimonthly) and calcium (1 g/day; n = 29) or double placebo (n = 27). Serum 25-hydroxyvitamin D concentrations as measured by radioimmunoassay, albumin-corrected calcium concentrations, and spot urinary calcium-creatinine ratios were determined monthly. RESULTS: No abnormalities in serum calcium concentration were observed. One participant who received placebo developed hypercalciuria. No group differences were seen in the change in CD4 count or CD4% or viral load during 12 months. The overall mean monthly serum 25-hydroxyvitamin D concentrations were higher in the group that received vitamin D and calcium than in the placebo group, as was the monthly serum 25-hydroxyvitamin D area under the curve. After completing 12 months of study, 2 (6.7%) participants in the group that received vitamin D and calcium had a trough serum 25-hydroxyvitamin D concentration <20 ng/mL compared with 14 (50%) in the placebo group. Twelve (44.4%) in the group that received vitamin D and calcium had a trough serum 25-hydroxyvitamin D concentration of > or =30 ng/mL compared with 3 (11.1%) in the placebo group. CONCLUSIONS: Administration of oral cholecalciferol to HIV-infected children and adolescents at a dosage of 100,000 IU every 2 months, together with 1 g/day calcium, is safe and results in significant increases in serum 25-hydroxyvitamin D concentrations.

Insulin resistance, hepatic lipid and adipose tissue distribution in HIV-infected men.

BACKGROUND: A large proportion of HIV-infected patients on antiretroviral medication develop insulin resistance, especially in the context of fat redistribution. This study investigates the interrelationships among fat distribution, hepatic lipid content, and insulin resistance in HIV-infected men. METHODS: We performed a cross-sectional analysis of baseline data from 23 HIV-infected participants in three prospective clinical studies. Magnetic resonance spectroscopy was used to quantify hepatic lipid concentrations. Magnetic resonance imaging was used to quantify whole-body adipose tissue compartments: that is, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes, as well as the intermuscular adipose tissue (IMAT) subcompartment and the omental-mesenteric adipose tissue (OMAT) and retroperitoneal adipose tissue (RPAT) subcompartments of VAT. The homeostasis model for assessment of insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin concentrations. RESULTS: Hepatic lipid content correlated significantly with total VAT (r = 0.62, P = 0.0014), but not with SAT (r = 0.053, P = 0.81). In univariate analysis, hepatic lipid content was associated with the OMAT (r = 0.67, P = 0.0004) and RPAT (r = 0.53, P = 0.009) subcompartments; HOMA-IR correlated with both VAT and hepatic lipid contents (r = 0.61, P = 0.057 and r = 0.68, P = 0.0012, respectively). In stepwise linear regression models, hepatic lipid had the strongest associations with OMAT and with HOMA-IR. CONCLUSION: Hepatic lipid content is associated with VAT volume, especially the OMAT subcompartment, in HIV-infected men. Hepatic lipid content is associated with insulin resistance in HIV-infected men. Hepatic lipid content might mediate the relationship between VAT and insulin resistance among treated, HIV-infected men.

Independent associations of insulin resistance with high whole-body intermuscular and low leg subcutaneous adipose tissue distribution in obese HIV-infected women.

BACKGROUND: Obesity and insulin resistance are growing problems in HIV-positive (HIV+) women receiving highly active antiretroviral therapy (HAART). OBJECTIVE: The objective was to determine the contribution of adipose tissue (AT) enlargement and distribution to the presence of insulin resistance in obese HIV+ women. DESIGN: Whole-body intermuscular AT (IMAT), visceral AT (VAT), subcutaneous AT (SAT), and SAT distribution (leg versus upper body) were measured by whole-body magnetic resonance imaging. Insulin sensitivity (S(I)) was measured with an intravenous glucose tolerance test in obese HIV+ women recruited because of their desire to lose weight (n=17) and in obese healthy controls (n=32). RESULTS: The HIV+ women had relatively less whole-body SAT and more VAT and IMAT than did the controls (P<0.05 for all). A significant interaction by HIV status was observed for the relation of total SAT with S(I) (P<0.001 for the regression's slope interactions after adjustment for age, height, and weight). However, relations of IMAT, VAT, and SAT distribution (leg SAT as a percentage of total SAT; leg SAT%) with S(I) did not differ significantly between groups. For both groups combined, the best model predicting a low S(I) included significant contributions by both high IMAT and low leg SAT%, independent of age, height, and weight, and no interaction between groups was observed (overall r(2)=0.44, P=0.0003). CONCLUSION: In obese HIV+ women, high whole-body IMAT and low leg SAT% distribution are independently associated with insulin resistance.

Body composition and metabolic effects of a diet and exercise weight loss regimen on obese, HIV-infected women.

HIV has classically been a wasting disease. However, in the United States, obesity is increasingly common among HIV-infected individuals receiving effective antiviral treatment. The risks of obesity are unclear in HIV, although the increased prevalence of diabetes and cardiovascular disease in the presence or absence of obesity causes growing concern. This study aimed to assess the effects of weight loss (through energy restriction combined with aerobic and resistance exercise) on body composition, body fat distribution, resting energy expenditure, quality of life (QOL), strength and fitness, and metabolic risk factors in obese, HIV-infected women. Eighteen HIV-infected women with a body mass index of 30 or more completed a 12-week weight loss program. Before and after the intervention, body composition and fat distribution by dual energy x-ray absorptiometry and whole-body magnetic resonance imaging, resting energy expenditure by indirect calorimetry, QOL, strength, and fitness were measured. Insulin sensitivity by intravenous glucose tolerance test and circulating cardiovascular risk factors (including lipids, tissue plasminogen activator, and plasminogen activator inhibitor 1) were measured in a subset (n = 9). Daily food intake and total body weight decreased (mean +/- SD) by 3195 +/- 477 kJ and 6.7 +/- 4.2 kg, respectively. Weight lost was 95.5% fat by dual energy x-ray absorptiometry or 6.2 L of subcutaneous adipose tissue, 0.7 L visceral adipose tissue, and 0.8 L skeletal muscle by magnetic resonance imaging. Resting energy expenditure fell approximately 419 kJ, strength and fitness increased by 28.9% +/- 18.5% and 36.8% +/- 41.6%, respectively, and QOL improved in 11 of 13 dimensions. There was significant insulin resistance in the subset with metabolic measurements at baseline, and at follow-up there was no improvement in fasting glucose, insulin, or insulin sensitivity, nor was there any change in fasting lipids, tissue plasminogen activator, or plasminogen activator inhibitor 1. There was no significant change in CD4 count or HIV viral load. In conclusion, moderate weight loss achieved by a short-term program of diet and exercise in obese HIV-positive women appears safe and induces loss of adiposity in both the subcutaneous adipose tissue and visceral adipose tissue regions. Despite reduced food intake, weight and fat loss, as well as improvements in strength, fitness, and QOL, the lack of improvement in metabolic parameters suggests that additional interventions may be necessary to reduce the risk of diabetes and cardiovascular disease in this population.

Antiretroviral therapy affects the composition of weight loss in HIV infection: implications for clinical nutrition.

BACKGROUND: Weight loss is comprised of variable proportions of fat and fat-free mass (FFM). HIV-infected patients treated with antiretroviral (ARV) agents may lose subcutaneous fat (lipoatrophy) in the absence of FFM depletion, which could confound the clinical interpretation of weight loss. METHODS: We retrospectively analyzed the results of anthropometric and dual-energy X-ray absorptiometry studies in 196 HIV-infected men and women with documented 10% weight loss (HIV group), and compared them to 29 untreated, HIV-infected men without 10% weight loss (HIV weight-stable), and 109 healthy adults (72 men and 37 women) to evaluate the effect of ARV therapy on the composition of weight loss. The HIV group was divided into four subgroups according to current ARV therapy: treatment-naive (59 men and 26 women), nucleoside reverse transcriptase inhibitor (NRTI) monotherapy (45 men), dual NRTI therapy (28 men) and highly active ARV therapy (HAART) (19 men and 20 women). RESULTS: Ages and heights were similar in all groups, while body mass index (BMI) and body composition differed significantly. BMI was higher in HIV-infected men and women on HAART than in the other HIV groups, although less than in HIV weight-stable (P=0.36) and healthy controls (P<0.0005). Fat content was lower in all HIV groups than in controls (P<0.001), while FFM was similar in HIV-infected men and women on dual NRTI and HAART and in controls. Comparison with HIV weight-stable gave higher estimates of the contribution of FFM to the differences in weight. CONCLUSION: Treatment of HIV infection with ARV may affect the interpretation of 10% weight loss.

A comparison of abdominal subcutaneous adipose tissue pattern in obese and lean HIV-infected women.

Cells from the superficial and deep subcompartments of the abdominal subcutaneous adipose tissue (SAT) compartment have distinct metabolic activities in vitro. The effect of differing energy balance on the relative in vivo sizes of these subcompartments has not been reported. We retrospectively investigated the effects of obesity and leanness on the relative amounts of superficial and deep SAT in the bulky posterior abdominal adipose tissue in HIV(+) women. We studied the baseline results of MRI scans in 32 obese and 28 lean HIV-infected women. We also compared the change in response to specific interventions. Abdominal MRI slices were obtained at the L4-L5 and L2-L3 intervertebral spaces and were divided into anterior and posterior halves. The posterior portions were further subdivided into deep (PDSAT) and superficial layers (PSSAT) based on tissue planes visible on the MRI. Fat areas in adjacent landmark levels at the trochanter and anterior superior iliac spine were also obtained. PDSAT was larger at L4-L5 than at L2-L3 in both the lean and obese groups. PDSAT was larger than PSSAT at L4-L5 in obese women, and there was preferential loss of PDSAT in obese women who completed a 12-wk energy-deficit diet and exercise program. The contents of PDSAT and PSSAT did not differ in the lean group, and proportional increases in both SAT subcompartments were noted in response to weight gain. In summary, obesity is associated with a preferential increase in PDSAT and greater loss in PDSAT after weight loss. This study defines distinct metabolism responses in fat subcompartments.

Validation of an elliptical anthropometric model to estimate visceral compartment area.

OBJECTIVE: The visceral compartment is a surrogate for visceral adipose tissue. Cross-sectional visceral compartment area (VCA) has been approximated from waist circumference using a circular model. However, the two-dimensional shape of the abdomen is rarely circular. This study validated an elliptical model of cross-sectional total abdominal area (TAA), subcutaneous adipose tissue (SAT) area, and VCA at the L(4)-L(5) level. RESEARCH METHODS AND PROCEDURES: We analyzed magnetic resonance images (MRIs) at the level of the L(4)-L(5) intervertebral space from 35 subjects with a wide range of abdominal adiposity. Waist circumference, abdominal thickness (midline sagittal diameter), abdominal width (coronal diameter at one-half of abdominal thickness), and abdominal SAT thickness at four sites (front, back, right, and left) were measured from MRI images using an image analysis software. The same anatomical regions were also estimated from anthropometrics purely by geometric formulae of circular and elliptical models. A simple linear regression model was used to interpret the association strength between anthropometric estimates and MRI measures. RESULTS: Estimated TAA by either model was strongly related to MRI TAA (r(2) = 0.98, p < 0.0001). The SAT and VCA by MRI analysis showed a stronger association with calculation from an elliptical model (r(2) = 0.95 and 0.88, respectively; p < 0.001) than a circular model (r(2) = 0.69 and 0.25, respectively; p < 0.001). The absolute prediction residuals and variances were significantly smaller with an elliptical model than a circular model (p < 0.0001). DISCUSSION: An elliptical anthropometric model might be superior to a circular model to estimate abdominal SAT and VCA.

Increased systemic and adipose tissue cytokines in patients with HIV-associated lipodystrophy.

The lipodystrophy syndrome (adipose tissue redistribution and metabolic abnormalities) observed with highly active antiretroviral therapy (HAART) during human immunodeficiency virus (HIV) infection may be related to increased proinflammatory cytokine activity. We measured acute cytokine (TNF-alpha, IL-6, leptin), glycerol, and lactate secretion from abdominal subcutaneous adipose tissue (SAT), and systemic cytokine levels, in HIV-infected subjects with and without lipodystrophy (HIVL+ and HIVL-, respectively) and healthy non-HIV controls. Lipodystrophy was confirmed and characterized as adipose tissue redistribution in HIVL+ compared with HIVL- and controls, by dual-energy X-ray absorptiometry and by whole body MRI. TNF-alpha secretion from abdominal SAT and circulating levels of IL-6, soluble TNF receptors I and II, and insulin were elevated in HIVL+ relative to HIVL- and/or controls, particularly in HIVL+ undergoing HAART. In the HIV-infected group as a whole, IL-6 secretion from abdominal SAT and serum IL-6 were positively associated with visceral fat and were negatively associated with the relative amount of lower limb adipose tissue (P < 0.01). Decreased leptin and increased lactate secretion from abdominal SAT were specifically associated with HAART. In conclusion, increased cytokine secretion from adipose tissue and increased systemic proinflammatory cytokine activity may play a significant role in the adipose tissue remodeling and/or the metabolic abnormalities associated with the HIV-lipodystrophy syndrome in patients undergoing HAART.

Studies of adipose tissue metabolism in human immunodeficiency virus-associated lipodystrophy.

We studied aspects of metabolism in subcutaneous adipose tissue (SAT) in 40 human immunodeficiency virus (HIV)-infected subjects with and without lipodystrophy and in healthy control subjects. HIV-infected subjects without lipodystrophy had less SAT and visceral adipose tissue (VAT). Glycerol release was higher in both HIV-infected groups, especially those without fat redistribution. Tumor necrosis factor (TNF) release from SAT and serum soluble TNF receptor 2 concentrations were significantly higher in HIV-infected individuals with lipodystrophy. The absolute production of acylation-stimulating protein (ASP) and the percentage conversion of the complement protein to ASP were significantly lower in HIV-infected subjects with lipodystrophy. Further studies are needed to dissect the factors that mediate lipoatrophy in HIV infection.